Comparing the Vascular Thromboembolic Events Following

Zhou et al. BMC Nephrology (2018) 19:376 https://doi.org/10.1186/s12882-018-1166-0

RESEARCHARTICLE Open Access Comparing the vascular thromboembolic events following arteriovenous fistula in Chinese population with end-stage renal diseases receiving Clopidogrel versus Beraprost sodium therapy: a retrospective cohort study Yu Zhou1†, Ling Du2†,BoTu3, Qiquan Lai1, Xiaonan Du2†,BoXu4, Fan Zhang5, Mingdong Zhao6*, Ziming Wan1* and Jiajie Lai7*

Abstract Background: To assess the time to first on-study vascular thromboembolic events (VTEs) of clopidogrel (CL) or beraprost sodium (BPS) in Chinese population with end-stage renal disease (ESRD) treated with arteriovenous fistula (AVF) surgery. Methods: From Jan 2009 to May 2015, 346 ESRD cases suffering an AVF surgery and undergoing oral administration of 75 mg CL (initial dose of 300 mg), 1 time/day, for 4 weeks or 40 μg BPS, 3 times/day, for 4 weeks were retrospectively assessed. The primary outcome was time to first on-study VTE. Results: In total, 222 ESRD cases (CL, n = 112; BPS, n = 110) were assessed, with a median follow-up time of 38.1 months (range, 37–40 months). The mean time to first on-study VTE was 1.2 weeks (0.5–2.3) and 1.8 weeks (1.2–3.8) for CL and BPS, respectively (HR 0.27, 95% CI 0.16–1.45; P = 0.00). An increased incidence of VTEs was found during the 1th-month follow-up, with rates of 14.2 and 5.5% for CL and BPS, respectively (P = 0.03). The difference persisted over time, with rates of 24.1 and 11.8% at final follow-up, respectively (P = 0.02). Conclusion: CL with an increased risk of VTEs tended to have a VTE within the 1st month after cessation compared with BPS. Keywords: Clopidogrel, Beraprost sodium, Vascular thromboembolic event, Arteriovenous fistula, Chinese population

* Correspondence: [email protected]; [email protected]; [email protected] †Yu Zhou, Ling Du and Xiaonan Du contributed equally to this work. 6Department of Orthopaedics, Jinshan Hospital, Fudan University, Longhang Road No. 1508, Jinshan District, Shanghai 201508, China 1Department of Nephrology, The First Affiliated Hospital of Chongqing Medical University, Youyi Road No.1, Yuzhong District, Chongqing 400016, China 7Department of Gynaecology and obstetrics, The First Affiliated Hospital of Sun Yat-sen University, Huangpu East Road No. 183, Huangpu District, Guangzhou 510700, China Full list of author information is available at the end of the article

© The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Zhou et al. BMC Nephrology (2018) 19:376 Page 2 of 7

Background clinical data which might lead to informative censoring Establishing and maintaining long-term vascular access is for time to first on-study VTEs; loss of follow-up; a prerequisite for hemodialysis in patients with end-stage interruption or modification of BPS or CL regimen; renal disease (ESRD) [1–4]. An ideal vascular access dropout owing to or severe infection; life expectancy less should provide sufficient blood flow for hemodialysis to than 2 years; concomitant mental illness; an American ensure the completion of hemodialysis procedures, as well Society of Anesthesiologists (ASA) score of IV or V. Pa- as long enough use time and as few complications as tients would be censored at any time when they were loss possible, which is an important condition for sustaining to follow-up for the follow-up period, for whatever reason. long-term survival [5]. During the treatment of arterioven- Data collection for these cases was censored at completion ous fistula (AVF), it is possible that anastomotic embolism of the study. can often lead to failure of fistula [6, 7]. Therefore, long-term dialysis patients have to face treatment trouble Surgical technique and mental pain [8, 9]. ESRD patients are considered at Preoperatively, the arteries with strong fluctuation and increased risk for vascular thromboembolic events (VTEs) thick veins were marked. After local anesthesia, the lon- after an AVF surgery [6]. The use of antiplatelet medica- gitudinal incision of the skin was performed in the view tions, specifically clopidogrel (CL) and beraprost sodium of the microscope for 1.5–2 cm, following by exposure, (BPS), is steadily increasing [10, 11]. Previous studies show dissociation of cephalic vein and artery. The distal end that patients receiving either of these medications are at of the cephalic vein was ligated. After the expansion of decreased risk for VTEs after an AVF surgery, but the risk the proximal cephalic vein, the intravenous injection of in a large, generalizable Chinese population is unknown heparin saline is used to test whether the cephalic vein [12, 13]. To our knowledge, a direct comparison between is obstructed or not. The 45 ° Angle pruning of the anas- CL and BPS has rarely been reported in the previous litera- tomosis was performed. The peripheral membrane of ture. Despite poor efficacy in ESRD patients, BPS and CL the vascellum was clipped and the vascellum was repeat- remain promising options to decrease AVF-related VTEs. edly washed with heparin saline. The radial artery Nevertheless, several unanswered questions remain. between the vascular clamps was distended by injection The aim of this study was to assess the outcome of CL of heparin saline with a fine needle. The radial artery or BPS using time to first on-study VTEs as the primary was opened longitudinally with a sharp knife, about 4–5 endpoint in ESRD cases suffering an AVF surgery in mm in length. End-to-side continuous anastomosis of Chinese population to further improve the design of the the cephalic vein and radial artery was performed in line therapeutic regime. with relatively mature surgical techniques [15, 16]. Anas- tomoses were formed using 8.0 prolene. It should be Methods noted that blood vessels should not be warped or sub- Study population jected to pressure. During the suture process, the needle All ESRD cases who were diagnosed according to stand- spacing should be as consistent as possible. After the ard criteria [14] and underwent an AVF surgery, follow- completion of the anastomosis, the arterial clip was re- ing by peroral administration of 40 μg BPS(Beijing Ted leased and then clamped, followed by the intravenous Pharmaceutical Co., LTD., China, drug specifications: clip. After 5 min, all the vascular clips were released. A 20 μg), 3 times per day, for 1 month or 75 mg CL (initial small amount of blooding at the vascular anastomosis dose of 300 mg, Hangzhou Sanofi Pharmaceutical Co., point can be gently pressed to stop the bleeding. LTD., China, drug specifications: 75 mg), 1 time per day, for 1 month were identified from three medical centers Definitions of main descriptive variables (Jinshan Hospital, Fudan University; the First Affiliated The primary endpoint was time to first on-study VTEs. Hospital, Sun Yat-sen University; the First Affiliated Hos- Prior to the start of the study, an Endpoint Judgment pital of Chongqing Medical University) between Jan 2009 Committee (EJC) that comprised of 3 independent and May 2015. Inclusion criteria: age ranging 20–50 years; ultrasound doctors who are not involved directly in the within 4 weeks prior to surgery, no cardiovascular-related study was established in each institution. VTEs were medications were applied in any case; dialysis was defined as an interruption of blood flow owing to performed for 3 times/week, 3~4 h/time. Main exclusion anastomosis-related stenosis or thrombus, which was criteria: chronic wasting disease; myelodysplastic syn- determined by an EJC based on colour Doppler ultra- drome; cardiovascular dynamic instability; coagulopathy; sonography. Primary patency at the anastomoses was hemorrhagic endovasculitis; a long-term history of defined as the interval from the time of access to any receiving the BPS or CL treatment; deterioration of renal intervention which involved in restoring or sustaining function during follow-up; co-occurring tumour; Child- patency. Patency was censored by three independent Turcotte-Pugh classification of C for liver function; ultrasound doctors at the date of on-study VTE survey. Zhou et al. BMC Nephrology (2018) 19:376 Page 3 of 7

A venous diameter greater than 5 mm can be adapted to in the CL-treated cohort. However, it failed to be ob- the need for dialysis and is not easily clogged. The served or was not apparent in the BPS-treated cohort. success rate of internal fistula = patency number/total num- During the 1st month after cessation, 6 patients (3/110) ber *100%. The analysis of the rate for time to first and had a VTE; during the 2nd month, 2 (2/110) underwent subsequent on-study VTEs is basedonanAndersen-Gill a VTE; from 3rd month to data cut-off, 5 (5/110) under- model [17]. Major bleeding events were defined as prior went a VTE. A decrease risk of VTEs by 47% was de- statements [18]. tected in BPS compared with CL (HR, 2.04; 95% CI 0.12–2.17; P = 0.001), as presented in Table 3 and Fig. 2. Statistical analysis The data up to the primary analysis cut-off were valid Adverse events data. Categorical variables were expressed as frequencies A major bleeding event happened among 5.4% of and percentages. Quantitative variables are presented as CL-treated cohort; and such event occurred in 4.5% of either the mean +/− standard deviation (SD) or median BPS-treated cohorts (P = 0.78). Compared with BPS, CL [interquartile range (IQR)] depending on the data distri- was not associated with an increased risk in major bleed- bution. Bivariate analyses involving ANOVA and ing (HR1.06; 95%CI: 0.62–1.74). No significant differ- Chi-square tests were applied as appropriate to assess ences were detected in other adverse events. between-group differences. The Kaplan-Meyer analysis were constructed to exhibit the incidence of the primary Discussion study endpoint. In computations of event rates, In the current study evaluating time to first on-study follow-up time was censored at lost to follow up or VTE among at-risk ESRD patients undergoing an AVF all-cause death. All- cause death was ascertained until surgery, to our knowledge the largest AVF study to date, the end date of the data cut-off. The Cox regression the major finding was that BPS demonstrated superiority models was used to assess hazard ratio (HR). A P < 0.05 to CL by decreasing the occurrence of VTEs (primary was considered significantly different. Statistical analysis endpoint) in ESRD patients who underwent an AVF sur- is processed by IBM-SPSS (version 24.0, Inc., NY, USA). gery. Notably, CL tended to result in a first on-study VTE within the 1st month after the cessation of drug Results administration compared with BPS. Baseline characteristics At the study start, we hypothesized that excellent pri- During the study period, 346 consecutive ESRD cases mary endpoint would be attributed to CL on account of who underwent an AVF surgery and received peroral ad- several previous findings. Unfortunately, in our study, ministration of CL or BPS were identified. Of 346, 222 CL was inclined to lead to an increased risk of first cases (CL, n = 112; BPS, n = 110) met criteria. Details are on-study VTEs, which seemed to contradict its predict- summarized in Fig. 1. Follow-up regarding the primary ive efficacy of VTEs. The reasons for the finding remain endpoint was completed in August 2016. Median indistinct and can be elaborated different versions in follow-up time is 38.1 months (range, 37–40). Patient-re- some recent studies in ESRD patients who underwent lated baseline data are showed in Table 1.No an AVF surgery [10, 11]. An explanation for the opposite between-group significant differences were detected in finding is unhesitatingly unavailable, although CL which medical related diseases following the initiation of drug is commonly used to prevent ATEs might contribute to intervention. Patient-related baseline characteristics were the difference [19]. The occurrence of VTEs remains a well balanced. life-threatening clinical challenge, although considerable benefits of CL have been showed in previous clinical VTE incidence trials [20–22]. Thus far, several literatures have shown The rates of the VTEs for the CL and BPS groups were the negative impact of CL variability on VTEs in ESRD 24.1% (27/112) and 11.8% (13/110), respectively (Table 2). patients who underwent an AVF surgery, regardless of The mean time to first on-study VTE was 1.2 weeks the prevention of heart attack and strokes in cardiovas- (0.5–2.3) and 1.8 weeks (1.2–3.8) for CL and BPS, re- cular cases [23, 24]. Undeniably, our study underscored spectively (HR 0.27, 95% CI 0.16–1.45; P = 0.00). the potential CL-related risks that CL adopted in ESRD CL tended to have a higher incidence of VTEs in com- patients, which, compared with BPS, tended to be asso- parison with BPS at final follow-up (27 vs. 13, respect- ciated with a poor prognosis. ively). During the 1st month after cessation, 16 (16/112) There is a body of evidence suggesting that poor cases were diagnosed with a VTE; During the 2nd vascular elasticity and endovascular stenosis underlie a month, 3 underwent a VTE (3/112); Between 3rd month significant proportion of patients of VTEs [25, 26]. and data cut-off, 8 suffered a VTE (8/112). There is a Endometrial damage following an AVF surgery can con- distributed phenomenon of VTEs within the 1st month tribute to the occurrence of VTEs [25, 27]. In terms of Zhou et al. BMC Nephrology (2018) 19:376 Page 4 of 7

From Jan 2009 to May 2015, 346 ESRD cases suffering an AVF surgery and undergoing oral administration of 75 mg CL (initial dose of 300 mg), 1 time/ day, for 4 weeks or 40 µg BPS, 3 times/day, for 4 weeks

-Child-Turcotte-Pugh classification of C for liver Reasons for exclusion(n = 124) function(n = 7) -chronic wasting disease(n = 3) -clinical data which might lead to informative -myelodysplastic syndrome(n = 4) censoring for time to first on-study VTEs(n = -cardiovascular dynamic instability(n = 3) 13) -coagulopathy(n = 2) -loss of follow-up(n = 17) -hemorrhagic endovasculitis(n = 5) -interruption or modification of BPS or CL -a long-term history of receiving the BPS or CL regimen(n=11) treatment(n = 11) -dropout owing to or severe infection(n = 16) -deterioration of renal function during follow- -life expectancy < 2 year(n = 9) up(n = 4) -concomitant mental illness(n = 4) -co-occurring tumour(n = 12) -ASA score of IV or V(n = 3)

Eligible for final analysis(n = 222)

Group CL(n = 112) Allocation Group BPS(n = 110)

Lost to follow-up Follow-up Lost to follow-up 1months postoperatively 1 months postoperatively -Died of infectious disease(n = 1) -Died of death stroke(n = 1) -Died of cardiovascular disease(n = 2) -Died of cardiovascular disease(n = 3) -Died of hypertensive complications(n = -Died of hypertensive complications(n = 2) 1) 2 months postoperatively -Died of infectious diseases(n = 2) -Died of cardiovascular disease(n = 1) 2 months postoperatively -Died of infectious diseases(n = 3) -Died of cardiovascular disease(n = 2) -Died of septicemia and malignant -Died of pulmonary inflammation(n = 1) lymphoma(n = 1) -Died of infectious disease(n = 1) 3 months postoperatively 3 months postoperatively -Died of septicemia and malignant -Died of infectious disease(n = 1) lymphoma(n = 2) -Died of diabetic complications(n = 2) -Died of death stroke(n = 1) -Died of cardiovascular disease(n = 1) -Died of infectious diseases(n = 2) -Died of hypertensive complications(n = -Died of diabetic diseases(n = 1) 2) -Died of cardiovascular disease(n = 2) subsequent follow-up subsequent follow-up -Died of high blood pressure -Died of hypertensive complications, complications, diabetic complications, cancer, diabetic complications, car car accidents, cancer, sepsis, pulmonary accidents, infectious diseases, drowning, inflammation, commit suicide(n = 19) and suicide(n = 12)

Group CL (n = 82) Final follow-up Group BPS (n = 74)

Fig. 1 Flow diagram demonstrating methods for the population-based identification to assess the time to first on-study vascular thromboembolic events (VTEs) of clopidogrel (CL) or beraprost sodium (BPS) in Chinese population with end-stage renal disease (ESRD) treated with arteriovenous fistula (AVF) the success rate, there are many substantial studies indi- comparable to the outcome of a previous meta analysis cated that BPS has contributed to the improvement of the [27]. Furthermore, consistent with previous studies [30, 31], success rate of AVFs in the ESRD patients compared with high VTEs which were detected in CL-treated cohort CL, although a finding at odds with trends was detected in were associated with an increased risk of thrombus several previous literatures [10, 28]. Nevertheless, the complication. superiority of BPS has gained increasing recognition, Our finding is inconsistent with several reports on the and low VTEs in BPS is most likely explained by BPS rate of VTEs [4, 5, 32, 33]. A previous study by Yuo was itself [29]. Although the success rate of VTEs in our a retrospective assessment only with a rather small num- study was lower than anticipated, our finding was ber of cases, and the study failed to have a control group Zhou et al. BMC Nephrology (2018) 19:376 Page 5 of 7

Table 1 Between-group comparison of baseline data Table 2 Between-group comparison of VTE incidence Variable CL (n = 112) BPS (n = 110) P - value Variable CL (n = 112) BPS (n = 110) P - value Age (y) 0.73*a Total incidence of VTEs 27/112 13/110 0.02*a 20–39 35 33 VTE incidence 40–59 44 42 During the first Mos 16/112 6/110 0.03*a 60–79 33 35 During the second 3/112 2/110 0.64a Mos Sex, No. M/F 60/52 59/51 0.99*b a c from the third Mos 8/112 5/110 0.41 Systolic BP (mmHg) 167.13 ± 31.47 166.87 ± 34.79 0.15* to data cut-off c Diastolic BP (mmHg) 102.52 ± 25.46 103.24 ± 23.47 0.22* CL clopidogrel, BPS beraprost sodium, VTEs vascular thromboembolic events, Hypertension, No. 82 84 0.59*b Mos month *Statistically significant values *c Hb (g/dL) 12.14 ± 1.35 12.36 ± 1.12 0.15 aAnalysed using the Chi-square test BUN (mg/dL) 43.37 ± 15.31 42.83 ± 17.68 0.16*c eGFR (ml/min/1.73 m2) 13.15 ± 3.43 13.45 ± 3.62 0.48*c of VTEs. In addition, although VTEs were not detected Creatinine (mg/dL) 10.71 ± 1.48 10.42 ± 1.32 0.27*c in other cases with ESRD during the study, treatment in Dialysis duration 14.22 ± 7.35 14.68 ± 7.22 0.18*c accordance with guidelines is advocated to manage VTE with respective risk, and longer-term follow-up is necessary to ascertain access (months) any implications of the drug effect. Type dialysis, No. 0.37*b This study reflects the advantages of the relatively Haemodialysis 107 102 large sample size, which is inclined to provide statistical Peritoneal dialysis 5 8 power to identify insignificant differences in the primary Ambulatory status 0.47*a endpoint. The study excluded those cases with high risk for VTEs. Although such cases would be inclined to Normal walking 103 98 suffer a VTE, they also have a high rate of some other Walking with 912 complications, which could result in high rates of with- assistive devices drawal. Although our study has basically achieved the Completely 00 restricted walking desired results, as a retrospective study that BPS is a more optimistic for ESRD patients in preventing VTEs ASA level 0.94*a compared with CL, there are inevitably some limitations. 13134 Firstly, between-study comparisons might tend to be 24740 confounded by differences in population included. 33436 Secondly, surgeon- and patient- related confounders BMD −2.57 ± 0.34 −2.49 ± 0.52 0.47*c may be inevitable. Nevertheless, improvement in the BMI (kg/m2) 24.71 ± 4.34 25.12 ± 4.61 0.36*c success rate of VTEs remained noteworthy, which had been proved by the final logistic regression assessment Personal history of VTEs 16/112 18/110 0.67*b after adjusting some potentially and relatively imbal- b Family history of VTEs 12/112 14/110 0.64* anced variates. Diabetes mellitus Duration, year 19 (4–26) 18 (5–24) 0.14*c Table 3 VTE risk ratio between groups Type 2, No. 27 29 0.70*b Variable CL (n = 112) BPS (n = 110) P - value Insulin use, No. 15 17 0.66*b Total VTE HR (95%CI) 6.98 3.42 0.001* CL clopidogrel, BPS beraprost sodium, BP blood pressure, Hb haemoglobin, (3.17-18.61) (1.46–8.53) BUN blood urea nitrogen, eGFR estimated glomerular filtration rate, ASA VTE HR (95%CI) American Society of Anesthesiologists, BMD bone mineral density, BMI body mass index, VTEs vascular thromboembolic events during 1st Mos 7.15 3.29 0.135* *No statistically significant values aAnalysed using the Mann-Whitney test (2.49-15.11) (1.21–6.67) b Analysed using the Chi-square test during 2nd Mos 26.58 24.37 0.181* cAnalysed using an Independent-Samples t-test (8.53-89.17) (7.64–101.72) [30]. Furthermore, in their study the divergent results from 3rd Mos to 19.36 14.15 0.214* cannot be explained. A growing but still very limited data cut-off (6.62-86.19) (5.13–86.24) body of literature has shown that BPS tended to result CL clopidogrel, BPS beraprost sodium, VTE vascular thromboembolic event, HR in VTEs compared with CL [19, 25]. This difference may hazard ratio, CI confidence interval, Mos month be attributed to improved monitoring and management *Statistically significant values Zhou et al. BMC Nephrology (2018) 19:376 Page 6 of 7

Authors’ contributions YZ, LD, BT, QL and BX performed the data collection and analysis and participated in manuscript writing. XD performed the database setup and statistical analysis. FZ, MZ and ZW performed the operations. YZ and JL participated in the study design and coordination and helped to draft the manuscript. All of the authors have read and approved the final manuscript.

Ethics approval and consent to participate The study was approved by the institutional ethics review boards (Jinshan Hospital, Fudan University; the First Affiliated Hospital, Sun Yat-sen University; the First Affiliated Hospital of Chongqing Medical University), and an exemp- tion for informed consent was obtained from these Investigational Ethical Review Boards.

Consent for publication Not applicable

Competing interests The authors declare that they have no competing interests.

Publisher’sNote Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Fig. 2 Kaplan–Meier estimates of vascular thromboembolic events (VTEs) of arteriovenous fistula (AVF) between groups. At the final Author details 1 follow-up, the incidence of VTEs was higher in the CL group than in Department of Nephrology, The First Affiliated Hospital of Chongqing Medical University, Youyi Road No.1, Yuzhong District, Chongqing 400016, the BPS group (P = 0.001 by Kaplan–Meier test). VTE-Free survival China. 2Department of Anesthesiology, The Central Hospital of Wuhan, (time to first on-study VTE) comparing clopidogrel (CL) versus Tongji Medical College, Huazhong University of Science and Technology, beraprost sodium (BPS) Gusao Road No. 16, Jianghan District, Wuhan 430014, Hubei, China. 3Department of Ultrasonography, The First Affiliated Hospital of Chongqing Medical University, Youyi Road No.1, Yuzhong District, Chongqing 400016, Conclusions China. 4Department of Thoracic surgery, The First Affiliated Hospital of Sun The study demonstrates, as anticipated, the superiority Yat-sen University, Huangpu East Road No. 183, Huangpu District, Guangzhou 510700, China. 5Radiology Department, The First Affiliated of BPS over CL in ESRD patients using time to first Hospital of Sun Yat-sen University, Huangpu East Road No. 183, Huangpu on-study VTE as the primary study endpoint regardless District, Guangzhou 510700, China. 6Department of Orthopaedics, Jinshan of the follow-up period. Compared with CL, BPS shows Hospital, Fudan University, Longhang Road No. 1508, Jinshan District, Shanghai 201508, China. 7Department of Gynaecology and obstetrics, The a decreased risk for VTEs, the long-term significance of First Affiliated Hospital of Sun Yat-sen University, Huangpu East Road No. which remains to be clarified. However, the superior effi- 183, Huangpu District, Guangzhou 510700, China. cacy of BPS in the current study offers preliminary evidence of a benefit–risk that corroborates its application Received: 8 January 2018 Accepted: 30 November 2018 in ESRD cases receiving an AVF surgery. References Abbreviations 1. Salako AA, Badmus TA, Igbokwe MC, David RA, Laoye A, Akinbola IA, et al. ASA: American Society of Anesthesiologists; AVF: Arteriovenous fistula; Experience with arteriovenous fistula creation for maintenance hemodialysis BMD: Bone mineral density; BMI: Body mass index; BP: Blood pressure; in a tertiary Hospital in South-Western Nigeria. Saudi J Kidney Dis Transpl. BPS: Beraprost sodium; BUN: Blood urea nitrogen; CI: Confidence interval; 2018;29(4):924–9. https://doi.org/10.4103/1319-2442.239628. CL: Clopidogrel; eGFR: Estimated glomerular filtration rate; EJC: Endpoint 2. Pataniappan S, Subbiah V, Gopalan VR, Kumar PV, Vinothan RJS. Judgment Committee; ESRD: End-stage renal disease; Hb: Haemoglobin; Observational study of the efficacy of supraclavicular brachial plexus block HR: Hazard ratio; IQR: Interquartile range; Mos: Month; SD: Standard for arteriovenous fistula creation. Indian J Anaesth. 2018;62(8):616–20. deviation; VTEs: Vascular thromboembolic events https://doi.org/10.4103/ija.IJA_293_18. 3. McGrogan DG, Stringer S, Cockwell P, Jesky M, Ferro C, Maxwell AP, et al. Acknowledgements Arterial stiffness alone does not explain arteriovenous fistula outcomes. 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Risk of heparin-induced immediate-type the study and collection, analysis, and interpretation of data and in writing hypersensitivity during arteriovenous fistula placement. Intern Med. 2018; the manuscript. 57(16):2365–9. https://doi.org/10.2169/internalmedicine.9705-17. 7. Douglass A, Allen C, Presson A, Sarfati MR, Griffin CL, Smith BK, et al. Patient- Availability of data and materials reported outcomes in patients with end-stage renal disease: is quality of life The datasets used and/or analysed during the current study available from affected when catheters are used for hemodialysis versus arteriovenous the corresponding author on reasonable request. fistulas? J Vasc Surg. 2018;67(6):E200-E. https://doi.org/10.1016/j.jvs.2018.03.291. Zhou et al. BMC Nephrology (2018) 19:376 Page 7 of 7

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Antiplatelet agents for the prevention of arteriovenous fistula and graft